Release Time:2019-03-09  Hits:

Indexed by: Journal Article

Date of Publication: 2014-07-01

Journal: ASIAN PACIFIC JOURNAL OF CANCER PREVENTION

Included Journals: Scopus、PubMed、SCIE

Volume: 15

Issue: 18

Page Number: 7913-7917

ISSN: 1513-7368

Key Words: HDAC inhibitor; drug resistance; Beclin-1; autophagy; apoptosis

Abstract: Apoptotic cell death plays a predominant role in histone deacetylase (HDAC) inhibitor-induced cytotoxicity. Nuclear morphological changes and activation of apoptotic executors are involved in CTS203-induced cell death. However, emerging issues of HDAC inhibitor-resistance have been observed in patients. Herein, MCF-7 cells were continuously exposed to CTS203 until the derived cells could proliferate normally in its presence. The newly obtained CTS203-resistant cells were nominated as MCF-7/203R. Compared to MCF-7 original cells, the MCF-7/203R cells were less sensitive to CTS203-induced apoptosis, with a minimal 6-fold higher IC50 value. In contrast, the expression of Beclin-1 was dramatically up-regulated, positively correlated to the acquisition of CTS203-resistance. Our results revealed the participation of autophagy in acquired HDAC inhibitor-resistance and further identified Beclin-1 as a promising target for anti-drug resistance.